Treating myelomas

ABSTRACT

This document provides methods and materials related to treating myelomas. For example, methods and materials relating to the use of a composition containing albumin-containing nanoparticle/antibody complexes (e.g., ABRAXANE®/anti-CD38 polypeptide antibody complexes) to treat myelomas are provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 15/030,568 filed Apr. 19, 2016, which is a 35U.S.C. § 371 national phase application of PCT ApplicationPCT/US2015/035515 filed Jun. 12, 2015, which claims the benefit of U.S.Provisional Ser. No. 62/012,804, filed Jun. 16, 2014, the entirecontents of each of which are incorporated herein by reference.

BACKGROUND 1. Technical Field

This document relates to methods and materials involved in treatingmyelomas (e.g., multiple myeloma). For example, this document relates tomethods and materials involved in using complexes containingalbumin-containing nanoparticles (e.g., ABRAXANE® nanoparticles) andantibodies (e.g., anti-CD38 polypeptide antibodies such as Daratumumab,MOR202, or SAR650984) to treat myelomas.

2. Background Information

Multiple myeloma is a cancer of plasma cells. In multiple myeloma, agroup of plasma cells (myeloma cells) becomes cancerous and multiplies,raising the number of plasma cells to a higher than normal level. Inmany cases, multiple myeloma is detected as part of routine blood andurine tests.

SUMMARY

This document provides methods and materials involved in treatingmyelomas (e.g., multiple myeloma, light chain myeloma, and non-secretorymyeloma). For example, this document provides methods and materials forusing complexes containing albumin-containing nanoparticles (e.g.,ABRAXANE® nanoparticles) and antibodies (e.g., anti-CD38 polypeptideantibodies such as Daratumumab, MOR202, or SAR650984) to treat myelomas.

ABRAXANE® is available from Celgene Corp. and is a nanoparticleformulation that combines paclitaxel with human albumin. Anti-CD38polypeptide antibodies such as Daratumumab, MOR202, or SAR650984 areavailable from Johnson & Johnson/Genmab, Celgene Corp./Morphosys, orSanofi/Immunogen, respectively. Daratumumab is a monoclonal antibodyagainst CD38 polypeptides (see, e.g., de Weers et al., J. Immunol.,186(3): 1840-1848 (2011)).

As described herein, in vitro mixing of albumin-containing nanoparticles(e.g., ABRAXANE® nanoparticles) and antibodies (e.g., anti-CD38polypeptide antibodies such as Daratumumab, MOR202, or SAR650984) canresult in the formation of macromolecular complexes, the characteristicsof which (e.g., size, antibody content, or chemotherapeutic drugcontent) can be customized depending on need. In some cases, suchmacromolecular complexes can retain antibody mediated target bindingspecificity, can retain or exhibit enhanced chemotherapeutic tumor cellcytotoxicity, and can exhibit no additional toxicity beyond that ofABRAXANE® nanoparticles alone. As also described herein, contactingABRAXANE® with an anti-CD38 polypeptide antibody (e.g., Daratumumab,MOR202, or SAR650984) prior to administration to a human (e.g., a humanmyeloma cancer patient) can result in a complex that, when administeredas a complex, has an increased ability to treat myeloma as compared to atreatment regimen that includes administering ABRAXANE® and theanti-CD38 polypeptide antibody separately in a manner that does not formABRAXANE®/anti-CD38 polypeptide antibody complexes.

The methods and materials provided herein can be used to increase theprogression-free survival rate in myeloma patients. Increasingprogression-free survival can allow myeloma cancer patients to livelonger.

In general, one aspect of this document features a method for treating amammal having myeloma. The method comprises, or consisting essentiallyof, administering to the mammal a composition comprising nanoparticlescontaining albumin and paclitaxel complexed with an anti-CD38polypeptide antibody under conditions wherein the length ofprogression-free survival is increased. The mammal can be a human. Themyeloma can be multiple myeloma. The composition can compriseDaratumumab, MOR202, or SAR650984 complexed with the nanoparticles. Thecomposition can comprise an alkylating agent complexed with thenanoparticles. The alkylating agent can be a platinum compound. Theplatinum compound can be carboplatin. The anti-CD38 polypeptide antibodycan be a humanized antibody. The anti-CD38 polypeptide antibody can be achimeric antibody. The composition can be administered by injection. Theprogression-free survival can be increased by 15 percent. Theprogression-free survival can be increased by 25 percent. Theprogression-free survival can be increased by 50 percent. Theprogression-free survival can be increased by 75 percent. Theprogression-free survival can be increased by 100 percent. Thecomposition can be administered under conditions wherein the time toprogression is increased.

In another aspect, this document features a method for treating a mammalhaving myeloma. The method comprises, or consists essentially of,administering, to the mammal, a composition comprisingalbumin-containing nanoparticle/antibody complexes, wherein the averagediameter of the complexes is between 0.1 and 0.9 μm, and wherein theantibody is an anti-CD38 antibody. The mammal can be a human. Themyeloma can be multiple myeloma. The albumin-containingnanoparticle/antibody complexes can be ABRAXANE®/Daratumumab, MOR202, orSAR650984 complexes. The composition or the albumin-containingnanoparticle/antibody complexes can comprise an alkylating agent. Thealkylating agent can be a platinum compound. The platinum compound canbe carboplatin. The composition can comprise an anti-inflammatory agent.The anti-CD38 polypeptide antibodies can be humanized antibodies. Theanti-CD38 polypeptide antibodies can be chimeric antibodies. Thecomposition can be administered by injection. The administration of thecomposition can be effective to increase progression-free survival by 25percent. The administration of the composition can be effective toincrease progression-free survival by 50 percent. The administration ofthe composition can be effective to increase progression-free survivalby 75 percent. The administration of the composition can be effective toincrease progression-free survival by 100 percent. The administration ofthe composition can be under conditions wherein the median time toprogression for a population of mammals with the myeloma is at least 150days. The administration of the composition can be under conditionswherein the median time to progression for a population of mammals withthe myeloma is at least 165 days. The administration of the compositioncan be under conditions wherein the median time to progression for apopulation of mammals with the myeloma is at least 170 days. The averagediameter of the complexes can be from 0.1 μm to 0.3 μm. The averagediameter of the complexes can be from 0.15 μm to 0.3 μm. The averagediameter of the complexes can be from 0.2 μm to 0.5 μm. The averagediameter of the complexes can be from 0.3 μm to 0.5 μm. The averagediameter of the complexes can be from 0.2 μm to 0.8 μm. The averagediameter of the complexes can be from 0.2 μm to 0.7 μm.

In another aspect, this document features a method for treating a mammalhaving myeloma. The method comprises, or consists essentially of,administering, to the mammal, a composition comprisingalbumin-containing nanoparticle/antibody complexes, wherein the averagediameter of at least 5 percent of the complexes of the composition isbetween 0.1 and 0.9 μm, and wherein the antibodies are anti-CD38antibodies. The mammal can be a human. The myeloma can be multiplemyeloma. The albumin-containing nanoparticle/antibody complexes can beABRAXANE®/Daratumumab, MOR202, or SAR650984 complexes. The compositionor the albumin-containing nanoparticle/antibody complexes can comprisean alkylating agent. The alkylating agent can be a platinum compound.The platinum compound can be carboplatin. The composition can comprisean anti-inflammatory agent. The anti-CD38 polypeptide antibodies can behumanized antibodies. The anti-CD38 polypeptide antibodies can bechimeric antibodies. The composition can be administered by injection.The administration of the composition can be effective to increaseprogression-free survival by 25 percent. The administration of thecomposition can be effective to increase progression-free survival by 50percent. The administration of the composition can be effective toincrease progression-free survival by 75 percent. The administration ofthe composition can be effective to increase progression-free survivalby 100 percent. The administration of the composition can be underconditions wherein the median time to progression for a population ofmammals with the myeloma is at least 150 days. The administration of thecomposition can be under conditions wherein the median time toprogression for a population of mammals with the myeloma is at least 165days. The administration of the composition can be under conditionswherein the median time to progression for a population of mammals withthe myeloma is at least 170 days. The average diameter of at least 5percent of the complexes of the composition can be from 0.2 μm to 0.9μm. The average diameter of at least 5 percent of the complexes of thecomposition can be from 0.2 μm to 0.8 μm. The average diameter of atleast 5 percent of the complexes of the composition can be from 0.2 μmto 0.7 μm. The average diameter of at least 5 percent of the complexesof the composition can be from 0.2 μm to 0.6 μm. The average diameter ofat least 5 percent of the complexes of the composition can be from 0.2μm to 0.5 μm. The average diameter of at least 5 percent of thecomplexes of the composition can be from 0.2 μm to 0.4 μm. The averagediameter of at least 10 percent of the complexes of the composition canbe between 0.1 and 0.9 μm. The average diameter of at least 50 percentof the complexes of the composition can be between 0.1 and 0.9 μm. Theaverage diameter of at least 75 percent of the complexes of thecomposition can be between 0.1 and 0.9 The average diameter of at least90 percent of the complexes of the composition can be between 0.1 and0.9 μm.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DETAILED DESCRIPTION

This document provides methods and materials involved in treatingmyelomas (e.g., multiple myeloma, light chain myeloma, and non-secretorymyeloma). For example, this document provides methods and materials forusing complexes containing albumin-containing nanoparticles (e.g.,ABRAXANE® nanoparticles) and antibodies (e.g., anti-CD38 polypeptideantibodies such as Daratumumab, MOR202, or SAR650984) to treat myelomas.

The methods and materials provided herein can be used to treat any typeof myeloma. For example, the methods and materials provided herein canbe used to treat multiple myeloma, light chain myeloma, or non-secretorymyeloma. In some cases, the methods and materials provided herein can beused to treat myelomas in any type of mammal including, withoutlimitation, mice, rats, dogs, cats, horses, cows, pigs, monkeys, andhumans.

In some cases, complexes containing albumin-containing nanoparticles(e.g., ABRAXANE® nanoparticles) and antibodies (e.g., anti-CD38polypeptide antibodies such as Daratumumab, MOR202, or SAR650984) can bedesigned to have an average diameter that is greater than 1 μm. Forexample, appropriate concentrations of albumin-containing nanoparticlesand antibodies can be used such that complexes having an averagediameter that is greater than 1 μm are formed. In some cases,manipulations such as centrifugation can be used to form preparations ofalbumin-containing nanoparticle/antibody complexes where the averagediameter of those complexes is greater than 1 μm. In some cases, thepreparations of albumin-containing nanoparticle/antibody complexesprovided herein can have an average diameter that is between 1 μm and 5μm (e.g., between 1.1 μm and 5 μm, between 1.5 μm and 5 μm, between 2 μmand 5 μm, between 2.5 μm and 5 μm, between 3 μm and 5 μm, between 3.5 μmand 5 μm, between 4 μm and 5 μm, between 4.5 μm and 5 μm, between 1.1 μmand 4.5 μm, between 1.1 μm and 4 μm, between 1.1 μm and 3.5 μm, between1.1 μm and 3 μm, between 1.1 μm and 2.5 μm, between 1.1 μm and 2 μm, orbetween 1.1 μm and 1.5 μm). Preparations of albumin-containingnanoparticle/antibody complexes provided herein having an averagediameter that is between 1 μm and 5 μm can be administered systemically(e.g., intravenously) to treat myelomas located within a mammal's body.In some cases, the preparations of albumin-containingnanoparticle/antibody complexes provided herein can have an averagediameter that is between 5 μm and 50 μm (e.g., between 6 μm and 50 μm,between 7 μm and 50 μm, between 10 μm and 50 μm, between 15 μm and 50μm, between 20 μm and 50 μm, between 25 μm and 50 μm, between 30 μm and50 μm, between 35 μm and 50 μm, between 5 μm and 45 μm, between 5 μm and40 μm, between 5 μm and 35 μm, between 5 μm and 30 μm, between 5 μm and25 μm, between 5 μm and 20 μm, between 5 μm and 15 μm, or between 10 μmand 30 μm). Preparations of albumin-containing nanoparticle/antibodycomplexes provided herein having an average diameter that is between 5μm and 50 μm can be administered into a mammal's body.

In some cases, a preparation of albumin-containing nanoparticle/antibodycomplexes provided herein can have greater than 60 percent (e.g.,greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexeshaving a diameter that is between 1 μm and 5 μm (e.g., between 1.1 μmand 5 μm, between 1.5 μm and 5 μm, between 2 μm and 5 μm, between 2.5 μmand 5 μm, between 3 μm and 5 μm, between 3.5 μm and 5 μm, between 4 μmand 5 μm, between 4.5 μm and 5 μm, between 1.1 μm and 4.5 μm, between1.1 μm and 4 μm, between 1.1 μm and 3.5 μm, between 1.1 μm and 3 μm,between 1.1 μm and 2.5 μm, between 1.1 μm and 2 μm, or between 1.1 μmand 1.5 μm). Preparation of albumin-containing nanoparticle/antibodycomplexes provided herein having greater than 60 percent (e.g., greaterthan 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes with adiameter that is between 1 μm and 5 μm can be administered systemically(e.g., intravenously) to treat myelomas located within a mammal's body.In some cases, a preparation of albumin-containing nanoparticle/antibodycomplexes provided herein can have greater than 60 percent (e.g.,greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexeshaving a diameter that is between 5 μm and 50 μm (e.g., between 6 μm and50 μm, between 7 μm and 50 μm, between 10 μm and 50 μm, between 15 μmand 50 μm, between 20 μm and 50 μm, between 25 μm and 50 μm, between 30μm and 50 μm, between 35 μm and 50 μm, between 5 μm and 45 μm, between 5μm and 40 μm, between 5 μm and 35 μm, between 5 μm and 30 μm, between 5μm and 25 μm, between 5 μm and 20 μm, between 5 μm and 15 μm, or between10 μm and 30 μm). Preparation of albumin-containingnanoparticle/antibody complexes provided herein having greater than 60percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) ofthe complexes with a diameter that is between 5 μm and 50 μm can beadministered to a mammal having myeloma.

In some cases, complexes containing albumin-containing nanoparticles(e.g., ABRAXANE® nanoparticles) and antibodies (e.g., anti-CD38polypeptide antibodies such as Daratumumab, MOR202, or SAR650984) can bedesigned to have an average diameter that is less than 1 For example,appropriate concentrations of albumin-containing nanoparticles andantibodies (e.g., Daratumumab, MOR202, or SAR650984) can be used suchthat complexes having an average diameter that is less than 1 μm areformed. In some cases, the preparations of albumin-containingnanoparticle/antibody complexes provided herein can have an averagediameter that is between 0.1 μm and 1 μm (e.g., between 0.1 μm and 0.95μm, between 0.1 μm and 0.9 μm, between 0.1 μm and 0.8 μm, between 0.1 μmand 0.7 μm, between 0.1 μm and 0.6 μm, between 0.1 μm and 0.5 μm,between 0.1 μm and 0.4 μm, between 0.1 μm and 0.3 μm, between 0.1 μm and0.2 μm, between 0.2 μm and 1 μm, between 0.3 μm and 1 μm, between 0.4 μmand 1 μm, between 0.5 μm and 1 μm between 0.2 μm and 0.6 μm between 0.3μm and 0.6 μm, between 0.2 μm and 0.5 μm or between 0.3 μm and 0.5 μm).Preparations of albumin-containing nanoparticle/antibody complexesprovided herein having an average diameter that is between 0.1 μm and0.9 μm can be administered systemically (e.g., intravenously) to treatmyelomas located within a mammal's body.

In some cases, a preparation of albumin-containing nanoparticle/antibodycomplexes provided herein can have greater than 60 percent (e.g.,greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexeshaving a diameter that is between 0.1 μm and 0.9 μm (e.g., between 0.1μm and 0.95 μm, between 0.1 μm and 0.9 μm, between 0.1 μm and 0.8 μm,between 0.1 μm and 0.7 μm, between 0.1 μm and 0.6 μm, between 0.1 μm and0.5 μm, between 0.1 μm and 0.4 μm, between 0.1 μm and 0.3 μm, between0.1 μm and 0.2 μm, between 0.2 μm and 1 μm, between 0.3 μm and 1 μm,between 0.4 μm and 1 μm, between 0.5 μm and 1 μm, between 0.2 μm and 0.6μm, between 0.3 μm and 0.6 μm, between 0.2 μm and 0.5 μm, or between 0.3μm and 0.5 μm). Preparation of albumin-containing nanoparticle/antibodycomplexes provided herein having greater than 60 percent (e.g., greaterthan 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes with adiameter that is between 0.1 μm and 0.9 μm can be administeredsystemically (e.g., intravenously) to treat myeloma located within amammal's body.

In general, albumin-containing nanoparticles such as ABRAXANE® can becontacted with an antibody such as an anti-CD38 polypeptide antibody(e.g., Daratumumab, MOR202, or SAR650984) prior to administration to ahuman to form an albumin-containing nanoparticle/antibody complex (e.g.,an ABRAXANE®/anti-CD38 polypeptide antibody complex). Any appropriatealbumin-containing nanoparticle preparation and any appropriate antibodycan be used as described herein. For example, ABRAXANE® nanoparticlescan be used as described herein. Examples of antibodies that can be usedto form albumin-containing nanoparticle/antibody complexes as describedherein include, without limitation, Daratumumab, MOR202, and SAR650984.For example, an appropriate dose of ABRAXANE® and an appropriate dose ofDaratumumab, MOR202, or SAR650984 can be mixed together in the samecontainer. This mixture can be incubated at an appropriate temperature(e.g., room temperature, between 15° C. and 30° C., between 15° C. and25° C., between 20° C. and 30° C., or between 20° C. and 25° C.) for aperiod of time (e.g., about 30 minutes, or between about 5 minutes andabout 60 minutes, between about 5 minutes and about 45 minutes, betweenabout 15 minutes and about 60 minutes, between about 15 minutes andabout 45 minutes, between about 20 minutes and about 400 minutes, orbetween about 25 minutes and about 35 minutes) before being administeredto a cancer patient (e.g., a multiple myeloma patient). In some cases,ABRAXANE® can be contacted with an anti-CD38 polypeptide antibody byinjecting both ABRAXANE® and the anti-CD38 polypeptide antibody eitherindividually or as a pre-mixed combination into an IV bag containing anIV bag solution. The contents of the IV bag includingABRAXANE®/anti-CD38 polypeptide antibody complexes can be introducedinto the patient to be treated.

In some cases, albumin-containing nanoparticles such as ABRAXANE® can becontacted with an antibody such as an anti-CD38 polypeptide antibody(e.g., Daratumumab, MOR202, or SAR650984) to form albumin-containingnanoparticle/antibody complexes (e.g., ABRAXANE®/anti-CD38 polypeptideantibody complexes) that are stored prior to being administered to acancer patient (e.g., a myeloma patient). For example, a compositioncontaining albumin-containing nanoparticle/antibody complexes can beformed as described herein and stored for a period of time (e.g., daysor weeks) prior to being administered to a cancer patient.

Any appropriate method can be used to obtain albumin-containingnanoparticles such as ABRAXANE® and an antibody such as an anti-CD38polypeptide antibody. For example, ABRAXANE® can be obtained fromCelgene Corp. or as described elsewhere (U.S. Pat. No. 6,537,579).Daratumumab, MOR202, or SAR650984 can be obtained from Johnson &Johnson/Genmab, Celgene Corp./Morphosys, or Sanofi/Immunogen,respectively. See, also, de Weers et al., J. Immunol., 186(3): 1840-1848(2011)).

In some cases, the combination of an albumin-containing nanoparticlesuch as ABRAXANE® and an antibody such as anti-CD38 polypeptide antibodycan include one or more other agents such as an alkylating agent (e.g.,a platinum compound). Examples of platinum compounds that can be used asan alkylating agent include, without limitation, carboplatin(PARAPLATIN®), cisplatin (PLATINOL®), oxaliplatin (ELOXATIN®), andBBR3464. Examples of other agents that can be included within analbumin-containing nanoparticle/antibody complex provided hereininclude, without limitation, prednisone, dexamethasone, thalidomide,revlimid, pomalidomide, melphalan, bortezomib, cyclophosphamide,vincristine, bendamustine, lenalidomide, bevacizumab, carfilzomib,etoposide, and cytarabine. For example, an albumin-containingnanoparticle/antibody complex provided herein (e.g., ABRAXANE®/anti-CD38polypeptide antibody complex) can include bortezomib or thalidomide aspart of the complex.

Any appropriate method can be used to administer an albumin-containingnanoparticle/antibody complex provided herein (e.g., ABRAXANE®/anti-CD38polypeptide antibody complexes) to a mammal. For example, a compositioncontaining albumin-containing nanoparticle/antibody complexes such asABRAXANE®/anti-CD38 polypeptide antibody complexes can be administeredvia injection (e.g., subcutaneous injection, intramuscular injection,intravenous injection, or intrathecal injection).

Before administering a composition containing an albumin-containingnanoparticle/antibody complex provided herein (e.g., ABRAXANE®/anti-CD38polypeptide antibody complexes) to a mammal, the mammal can be assessedto determine whether or not the mammal has myeloma. Any appropriatemethod can be used to determine whether or not a mammal has myeloma. Forexample, a mammal (e.g., human) can be identified as having myelomausing standard diagnostic techniques

After identifying a mammal as having myeloma, the mammal can beadministered a composition containing albumin-containingnanoparticle/antibody complexes provided herein (e.g.,ABRAXANE®/anti-CD38 polypeptide antibody complexes). For example, acomposition containing ABRAXANE®/anti-CD38 polypeptide antibodycomplexes can be administered prior to or in lieu of other myelomatreatments (e.g., stem cell transplantation or radiation therapy). Insome cases, a composition containing albumin-containingnanoparticle/antibody complexes provided herein (e.g.,ABRAXANE®/anti-CD38 polypeptide antibody complexes) can be administeredfollowing stem cell transplantation or radiation therapy.

A composition containing albumin-containing nanoparticle/antibodycomplexes provided herein (e.g., ABRAXANE®/anti-CD38 polypeptideantibody complexes) can be administered to a mammal in any appropriateamount, at any appropriate frequency, and for any appropriate durationeffective to achieve a desired outcome (e.g., to increaseprogression-free survival). In some cases, a composition containingalbumin-containing nanoparticle/antibody complexes provided herein(e.g., ABRAXANE®/anti-CD38 polypeptide antibody complexes) can beadministered to a mammal having myeloma to reduce the progression rateof the myeloma by 5, 10, 25, 50, 75, 100, or more percent. For example,the progression rate can be reduced such that no additional cancerprogression is detected. Any appropriate method can be used to determinewhether or not the progression rate of myeloma is reduced. For example,the progression rate of myeloma can be assessed by assessing a patientat different time points and determining the amount of myeloma cellspresent or the amount of proteins produced by myeloma cells present.These amounts determined at different times can be compared to determinethe progression rate. After treatment as described herein, theprogression rate can be determined again over another time interval. Insome cases, the stage of cancer (e.g., multiple myeloma) after treatmentcan be determined and compared to the stage before treatment todetermine whether or not the progression rate was reduced.

In some cases, a composition containing albumin-containingnanoparticle/antibody complexes provided herein (e.g.,ABRAXANE®/anti-CD38 polypeptide antibody complexes) can be administeredto a mammal having myeloma under conditions where progression-freesurvival is increased (e.g., by 5, 10, 25, 50, 75, 100, or more percent)as compared to the median progression-free survival of correspondingmammals having untreated myeloma or the median progression-free survivalof corresponding mammals having myeloma treated with ABRAXANE® and anantibody (e.g., an anti-CD38 polypeptide antibody) without formingABRAXANE®/antibody complexes (e.g., without forming ABRAXANE®/anti-CD38polypeptide antibody complexes). In some cases, a composition containingalbumin-containing nanoparticle/antibody complexes provided herein(e.g., ABRAXANE®/anti-CD38 polypeptide antibody complexes) can beadministered to a mammal having myeloma to increase progression-freesurvival by 5, 10, 25, 50, 75, 100, or more percent as compared to themedian progression-free survival of corresponding mammals having myelomaand having received ABRAXANE® or an antibody (e.g., an anti-CD38polypeptide antibody) alone. Progression-free survival can be measuredover any length of time (e.g., one month, two months, three months, fourmonths, five months, six months, or longer).

In some cases, a composition containing albumin-containingnanoparticle/antibody complexes provided herein (e.g.,ABRAXANE®/anti-CD38 polypeptide antibody complexes) can be administeredto a mammal having myeloma under conditions where the 8-weekprogression-free survival rate for a population of mammals is 65% orgreater (e.g., 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%,77%, 78%, 79%, 80% or greater) than that observed in a population ofcomparable mammals not receiving a composition containingalbumin-containing nanoparticle/antibody complexes provided herein(e.g., ABRAXANE®/anti-CD38 polypeptide antibody complexes). In somecases, a composition containing albumin-containing nanoparticle/antibodycomplexes provided herein (e.g., ABRAXANE®/anti-CD38 polypeptideantibody complexes) can be administered to a mammal having myeloma underconditions where the median time to progression for a population ofmammals is at least 150 days (e.g., at least 155, 160, 163, 165, or 170days).

An effective amount of a composition containing albumin-containingnanoparticle/antibody complexes provided herein (e.g.,ABRAXANE®/anti-CD38 polypeptide antibody complexes) can be any amountthat reduces the progression rate of myeloma, increases theprogression-free survival rate, or increases the median time toprogression without producing significant toxicity to the mammal.Typically, an effective amount of ABRAXANE® can be from about 50 mg/m²to about 150 mg/m² (e.g., about 80 mg/m²), and an effective amount of ananti-CD38 polypeptide antibody such as Daratumumab, MOR202, or SAR650984can be from about 5 mg/kg to about 20 mg/kg (e.g., about 10 mg/kg or 375mg/m²). If a particular mammal fails to respond to a particular amount,then the amount of ABRAXANE® or anti-CD38 polypeptide antibody can beincreased by, for example, two fold. After receiving this higherconcentration, the mammal can be monitored for both responsiveness tothe treatment and toxicity symptoms, and adjustments made accordingly.The effective amount can remain constant or can be adjusted as a slidingscale or variable dose depending on the mammal's response to treatment.Various factors can influence the actual effective amount used for aparticular application. For example, the frequency of administration,duration of treatment, use of multiple treatment agents, route ofadministration, and severity of the myeloma may require an increase ordecrease in the actual effective amount administered.

The frequency of administration can be any frequency that reduces theprogression rate of myeloma, increases the progression-free survivalrate, or increases the median time to progression without producingsignificant toxicity to the mammal. For example, the frequency ofadministration can be from about once a month to about three times amonth, or from about twice a month to about six times a month, or fromabout once every two months to about three times every two months. Thefrequency of administration can remain constant or can be variableduring the duration of treatment. A course of treatment with acomposition containing ABRAXANE®/anti-CD38 polypeptide antibodycomplexes can include rest periods. For example, a compositioncontaining ABRAXANE®/anti-CD38 polypeptide antibody complexes can beadministered over a two week period followed by a two week rest period,and such a regimen can be repeated multiple times. As with the effectiveamount, various factors can influence the actual frequency ofadministration used for a particular application. For example, theeffective amount, duration of treatment, use of multiple treatmentagents, route of administration, and severity of the myeloma may requirean increase or decrease in administration frequency.

An effective duration for administering a composition provided hereincan be any duration that reduces the progression rate of myeloma,increases the progression-free survival rate, or increases the mediantime to progression without producing significant toxicity to themammal. Thus, the effective duration can vary from several days toseveral weeks, months, or years. In general, the effective duration forthe treatment of myeloma can range in duration from several weeks toseveral months. In some cases, an effective duration can be for as longas an individual mammal is alive. Multiple factors can influence theactual effective duration used for a particular treatment. For example,an effective duration can vary with the frequency of administration,effective amount, use of multiple treatment agents, route ofadministration, and severity of the myeloma.

A composition containing albumin-containing nanoparticle/antibodycomplexes provided herein (e.g., ABRAXANE®/anti-CD38 polypeptideantibody complexes) can be in any appropriate form. For example, acomposition provided herein can be in the form of a solution or powderwith or without a diluent to make an injectable suspension. Acomposition also can contain additional ingredients including, withoutlimitation, pharmaceutically acceptable vehicles. A pharmaceuticallyacceptable vehicle can be, for example, saline, water, lactic acid,mannitol, or combinations thereof.

After administering a composition provided herein to a mammal, themammal can be monitored to determine whether or not the myeloma wastreated. For example, a mammal can be assessed after treatment todetermine whether or not the progression rate of myeloma was reduced(e.g., stopped). As described herein, any method can be used to assessprogression and survival rates.

In some cases, a formulation of ABRAXANE®/Daratumumab, MOR202, orSAR650984 complexes described in Example 1 can be administered to ahuman myeloma patient as described in the methods set forth in Example3.

In some cases, nanoparticles containing albumin (e.g., nanoparticleswith an albumin shell) and an agent other than paclitaxel can be used asdescribed herein in place of or in combination with ABRAXANE®. Forexample, albumin-containing nanoparticles designed to carry a cancerchemotherapeutic agent can be used to form nanoparticle/anti-CD38polypeptide antibody complexes that can be used as described herein.Examples of such cancer chemotherapeutic agents include, withoutlimitation, cyclophosphamide, melphalan, bortezomib, lenalidomide,pomalidomide, thalidomide, Adriamycin, and vincristine.

In some cases, a composition can be formulated to include nanoparticlescontaining albumin (e.g., nanoparticles with an albumin shell) that areconjugated to an antibody, agent, or combination of antibodies andagents to form complexes for treating myeloma. For example, albuminnanoparticles can be formulated to include prednisone, dexamethasone,thalidomide, revlimid, pomalidomide, melphalan, bortezomib,cyclophosphamide, vincristine, bendamustine, lenalidomide, bevacizumab,carfilzomib, etoposide, cytarabine, or a combination thereof with orwithout including an anti-CD38 polypeptide antibody such as Daratumumab,MOR202, or SAR650984.

In some cases, nanoparticles containing albumin (e.g., nanoparticleswith an albumin shell) or a complex described herein (e.g.,ABRAXANE®/Daratumumab, MOR202, or SAR650984 complexes) can be formulatedto include one or more anti-chronic inflammation treatment agentsdesigned to reduce the global state of immune dysfunction and/or chronicinflammation present within a cancer patient. For example, steroidalanti-inflammatory agents (e.g., prednisone), non-steroidalanti-inflammatory agents (e.g., naproxen), lympho-depleting cytotoxicagents (e.g., cyclophosphamide), immune cell and/or cytokine targetingantibodies (e.g., infliximab), or a combination thereof can beincorporated into nanoparticles containing albumin orABRAXANE®/Daratumumab, MOR202, or SAR650984 complexes. In some cases,anti-IL-4 agents (e.g., anti-IL-4 antibodies), anti-IL-13 agents (e.g.,soluble IL-13 receptor), and combinations thereof can be incorporatedinto nanoparticles containing albumin or ABRAXANE®/Daratumumab, MOR202,or SAR650984 complexes.

Any appropriate method can be used to assess whether or not the globalstate of immune dysfunction and/or chronic inflammation was reducedfollowing an anti-chronic inflammation treatment. For example, cytokineprofiles (e.g., IL-4, IL-13, IL-4, IL-13, IL-5, IL-10, IL-2, andinterferon gamma) present in blood can be assessed before and after ananti-chronic inflammation treatment to determine whether or not theglobal state of immune dysfunction and/or chronic inflammation wasreduced.

The invention will be further described in the following examples, whichdo not limit the scope of the invention described in the claims.

EXAMPLES Example 1—Making ABRAXANE®/Daratumumab, MOR202, or SAR650984Complexes

ABRAXANE® is incubated with various increasing concentrations ofDaratumumab, MOR202, or SAR650984 to form ABRAXANE®/Daratumumab, MOR202,or SAR650984 complexes of increasing diameter. Ten milligrams ofABRAXANE® is reconstituted in 1 mL of Daratumumab, MOR202, or SAR650984at 0, 2, 4, 6, 8, and 10 mg/mL, and the mixture is incubated at roomtemperature for 30 minutes. After incubation, the distributions ofparticle sizes are determined with the Mastersizer 2000. The medianparticle size can range from 0.05 μm to 10 μm. The antibodyconcentration in which ABRAXANE® is incubated can impact the size of thenanoparticle. Manipulating the size of the particles can change thepharmacokinetics of the drug complex as well as its bio-distribution,which in turn can improve the clinical efficacy of the drug complex.

Example 2—Use of ABRAXANE®/Daratumumab, MOR202, or SAR650984 Complexesto Inhibit Myeloma Progression More Effectively than ABRAXANE® Alone,Anti-CD38 Polypeptide Antibody Alone, and the Sequential Use of anAnti-CD38 Polypeptide Antibody and ABRAXANE®

Female athymic nude mice are injected with 1×10⁶ myeloma cells.Treatments are administered about 21 days later. Mice are treated with(a) a single dose of 100 μL PBS on day 0, (b) a single dose ofDaratumumab, MOR202, or SAR650984 (12 mg/kg) on day 0, (c) a single doseof ABRAXANE® (30 mg/kg) on day 0, (d) a single dose of Daratumumab,MOR202, or SAR650984 (12 mg/kg) on day 0 followed by a single dose ofABRAXANE® (30 mg/kg) on day 1, or (e) a single dose of AD160 (equivalentto 30 mg/kg of ABRAXANE®) on day 0. The survival times are thendetermined.

The AD160 complexes are produced as follows. 10 mg ABRAXANE® isreconstituted in 2 mg of Daratumumab, MOR202, or SAR650984 in 500 μL0.9% saline and incubated for 1 hour at room temperature. Afterincubation, AD160 is brought to 1 mL with 0.9% saline. AD160 is furtherdiluted, and 100 μL is administered to mice at a dose equivalent to 12mg/kg Daratumumab, MOR202, or SAR650984 and 30 mg/kg ABRAXANE®. Averageparticle size for AD160 is about 160 nm.

Example 3—ABRAXANE®/Daratumumab, MOR202, or SAR650984 Complexes asTargeted Therapy for Myelomas

The treatment schedule for ABRAXANE®/Daratumumab, MOR202, or SAR650984complexes is repeated each month (every 28 days+/−3 days) or untildisease progression, patient refusal, or unacceptable toxicity (Table 1)with the indicated dose escalation scheme (Table 2) and dose limitingtoxicities (Table 3).

TABLE 1 Agent Dose Route Days ReRx ABRAXANE ®/ assigned IV over 60minutes 1, 8 Every Daratumumab, at time of (only 1^(st) dose; and 28MOR202, or registration subsequent doses 15 days* SAR650984 infused overcomplexes 30 minutes) *One treatment cycle = 28 days +/− 3 days

TABLE 2 Dose Escalation Scheme. Dose Level Dose (ABX) Dose (anti-CD38)−2  75 mg/m² 30 mg/m² −1 100 mg/m² 40 mg/m²  1* 125 mg/m² 50 mg/m²  2150 mg/m² 60 mg/m²  3 175 mg/m² 70 mg/m² *Starting dose.

TABLE 3 Dose Limiting Toxicities (DLT). Toxicity DLT DefinitionHematologic Grade 4 ANC, Grade 4 Hgb, or PLT < 25,000 Renal Serumcreatinine ≥ 2 times baseline Other nonhematologic ≥grade 3 as per NCICommon Terminology Criteria for Adverse Events (CTCAE) version 4.0Determination of Maximum Tolerated Dose (MTD)

The maximum tolerated dose is defined as the highest dose level amongthose tested where at most one out of six patients develops a DLT priorto the start of their second cycle of treatment and the next highestdose level is such that two out of a maximum of six patients treated atthis dose level developed a DLT prior to the start of their second cycleof treatment.

Enrollment and Determination of MTD

A minimum of two or a maximum of six patients are accrued to a givendose level. For dose level 1 (and if accrued to, dose levels-1 & -2),enrollment is temporarily halted after each patient has been enrolled inorder to gather acute adverse event data over the first cycle of theirtreatment. For dose levels 2 & 3, patients are accrued to these doselevels so that at any given time no more than two patients are receivingtheir first cycle of treatment and acute adverse event data over thefirst treatment cycle for all other patients treated at the current doselevel is known. If, at any time in the enrollment process, two patientstreated at the current dose level develop a DLT during the first cycleof treatment, enrollment is closed to that dose level. Enrollment isre-opened to the next lower dose level if fewer than six patients havebeen treated at that dose level. If none of the first three patientstreated at a given dose level develops a DLT during the first cycle oftreatment, enrollment to the dose level is closed and enrollment isreopen at next higher dose level. If there are no other higher doselevels to be tested, three additional patients are enrolled at thecurrent dose level to confirm MTD. If one of the first three patientstreated at a given dose level develops a DLT during the first cycle oftreatment, three additional patients are enrolled (sequentially) ontothe current dose level. If, at any time in the enrollment of these threeadditional patients, a patient develops a DLT, enrollment is closed tothis dose level. Enrollment is re-opened to the next lower dose level iffewer than six patients are treated at that dose level. If none of thesethree additional patients develops a DLT during the first cycle oftreatment, enrollment to this dose level is closed and enrollment isreopened at next higher dose level. If there are no other higher doselevels to be tested, this is considered the MTD.

For this protocol, the patient returns for evaluation and retreatment(at least every 28+/−3 days) according to the schedule. If a patientfails to complete the first cycle of treatment for reasons other thantoxicity, an additional patient is enrolled to replace this patient.

Dosage Modification Based on Adverse Events

The modifications in Table 4 are followed until individual treatmenttolerance is ascertained. If multiple adverse events (Table 5) are seen,dose is administered based on greatest reduction required for any singleadverse event observed. Dose modifications apply to the treatment givenin the preceding cycle and are based on adverse events observed sincethe prior dose.

TABLE 4 Dose Levels Based on Adverse Events. ABRAXANE ®/Daratumumab,MOR202, or SAR650984 complexes - Both drugs are reduced DoseAccompanying anti-CD38 Level ABX dose dose (40% of ABX dose) 2 175 mg/m²70 mg/m² −1 150 mg/m² 60 mg/m² 1 125 mg/m² 50 mg/m² −2 100 mg/m² 40mg/m² −2  75 mg/m² 30 mg/m² *Dose level 1 refers to the starting dose.

TABLE 5 Use Common Terminology Criteria for Adverse Events (CTCAE) v.4.0* unless otherwise specified CTCAE Category Adverse Event DoseReduction Investigations ANC < 1000 or Day 1: Hold until counts abovethese levels. PLT < 75,000 Day 8: Omit dose that day and retreat at samedose level on day 15 if counts have recovered. Day 15: Omit dose thatday. NOTE: if two consecutive cycles of therapy require omission of adose, subsequent treatment cycles should begin (day 1) at next lowerdose. AST or Day 1: Hold until resolved to <Grade 2 then reduce Alkalinedose by ONE dose level. Phosphatase ≥ If treatment needs to be held >4weeks, discontinue Grade 2 study treatment and go to event monitoring.Neurology disorders Neuropathy ≥Grade 2 Day 1: Hold until resolved to<Grade 2 then reduce dose by ONE dose level. Day 8 OR 15- Omit dose thatday. If resolved to <Grade 2 by next scheduled dose, then dose reduce byone level If treatment needs to be held >4 weeks, discontinue studytreatment and go to Event Monitoring All other non- ≥Grade 3 Day 1: Holduntil resolved to ≤Grade 2 then reduce hematologic dose by ONE doselevel. adverse events Day 8: Omit dose that day. If resolved to ≤Grade 2by day 15, then dose reduce by one level and retreat. Day 15: Omit dosethat day. NOTE: if two consecutive cycles of therapy require omission ofa dose, subsequent treatment cycles should begin (day 1) at next lowerdose. If treatment needs to be held >4 weeks, discontinue studytreatment and go to Event Monitoring Gastrointestinal Bowel Discontinueall study treatment and proceed to Disorders perforation EventMonitoring Bowel Obstruction Grade 1 Continue patient on study forpartial bowel obstruction NOT requiring medical intervention. Grade 2Hold for partial obstruction requiring medical intervention. If resolvedto Grade 0 within 4 weeks, treatment may be restarted. If treatmentneeds to be held >4 weeks, discontinue all study treatment and go toEvent Monitoring. Grade 3 or 4 For complete bowel obstruction,discontinue study treatment and proceed to Event Monitoring CardiacDisorders Hypertension ≥Grade 3 Hypertension should be treated as pergeneral practice. If hypertension (≥150/100) persists despite treatment,hold treatment until blood pressure is below this level If treatmentneeds to be held >4 weeks due to uncontrolled hypertension, discontinuestudy treatment and go to Event Monitoring. Left ventricular systolicfunction- Grade 3 Hold until resolution to Grade ≤1. If treatment needsto be held >4 weeks, discontinue all study treatment and go to EventMonitoring. Grade 4 Discontinue treatment and proceed to EventMonitoring Respiratory, thoracic Bronchopulmonary and mediastinaldisorders Hemorrhage ≥Grade 2 Discontinue all study treatment andproceed to Event Monitoring Coagulation Hemorrhage Grade 3 Hold untilALL of the following criteria are met: 1. Bleeding has resolved and Hbis stable. 2. There is no bleeding diathesis that would increase therisk of therapy. 3. There is no anatomic or pathologic condition thatcould increase the risk of hemorrhage recurrence. If treatment needs tobe held >4 weeks, discontinue study treatment and go to Event MonitoringPatients who experience a recurrence of Grade 3 hemorrhage are todiscontinue all study treatment and proceed to Event Monitoring. Grade 4Discontinue study treatment and proceed to Event Monitoring Bleedingdiathesis Grade 3 or 4 Discontinue study treatment and proceed to EventMonitoring Vascular Venous disorders thrombosis Grade 3 or Holdtreatment. If the planned duration of full- asymptomatic doseanticoagulation is <2 weeks, treatment should Grade 4 be held until thefull-dose anti coagulation period is over. If the planned duration offull-dose anticoagulation is >2 weeks, treatment may be resumed duringthe period of full-dose anticoagulation IF all of the criteria below aremet: The subject must have an in-range INR (usually 2-3) on a stabledose of warfarin, or on stable dose of heparin prior to restartingtreatment. The subject must not have pathological conditions that carryhigh risk of bleeding (e.g. tumor involving major vessels or otherconditions) The subject must not have had hemorrhagic events while onstudy If thromboemboli worsen/recur upon resumption of study therapy,discontinue treatment. Symptomatic Discontinue treatment and proceed toEvent Grade 4 Monitoring Arterial Discontinue treatment and proceed toEvent thrombosis Monitoring (Angina, myocardial infarction, transientischemic attack, cerebrovascular accident, or any other arterialthromboembolic events) ANY GradeAncillary Treatment/Supportive Care

Routine use of colony-stimulating factors (G-CSF or GM-CSF) is notrecommended. Prophylactic use of colony-stimulating factors during thestudy is not allowed. Therapeutic use in patients with seriousneutropenic complications such as tissue infection, sepsis syndrome,fungal infection, etc., may be considered at physician discretion.Recombinant erythropoietin to maintain adequate hemoglobin levels andavoid packed red blood cell transfusions is allowed.

Patients should receive full supportive care while on this study. Thisincludes blood product support, antibiotic treatment and treatment ofother newly diagnosed or concurrent medical conditions. All bloodproducts and concomitant medications such as antidiarrheals, analgesics,and anti-emetics received from the first administration of study drugsuntil 30 days after the final dose are to be recorded in the medicalrecord. Patients participating in phase I program clinical trials arenot to be considered for enrollment in any other study involving apharmacologic agent-(drugs, biologics, immunotherapy approaches, genetherapy) whether for symptom control or therapeutic intent.

Hypersensitivity Reactions

Patients do not require premedication prior to administration ofABRAXANE®/Daratumumab, MOR202, or SAR650984 complexes. In the unlikelyevent of a hypersensitivity reaction, treatment with antihistamines, H2blockers, and corticosteroids is recommended. Patients should bepre-medicated with the typical regimen for paclitaxel regimens forsubsequent cycles. In the unlikely event of a mild hypersensitivityreaction, premedication may be administered using the premedicationregimen the institution typically uses for solvent-based paclitaxel.

ABRAXANE®/Daratumumab, MOR202, or SAR650984 Complexes

ABRAXANE®/Daratumumab, MOR202, or SAR650984 complexes are prepared as ahazardous low risk product. ABRAXANE® is supplied as a white tooff-white lyophilized powder containing 100 mg of paclitaxel andapproximately 900 mg Albumin Human USP (HA) as a stabilizer in a 50 mL,single-use vial. Each vial of the lyophilized product is reconstitutedas set forth below. Unreconstituted ABRAXANE® is stored at controlledroom temperature in its carton. Reconstituted ABRAXANE® is usedimmediately.

The dose appropriate number of vials of Daratumumab, MOR202, orSAR650984 are obtained, and each vial is further diluted per thefollowing directions to 4 mg/mL. The dose appropriate number ofABRAXANE® (paclitaxel) 100 mg vials is obtained and each vial isreconstituted per the following directions to a final concentrationcontaining 10 mg/mL nanoparticle albumin-bound (nab) paclitaxel. It isnot a requirement to use filter needles in the preparation of, orin-line filters during administration. In addition, filters of pore-sizeless than 15 micrometers are to be avoided.

As with other cytotoxic anticancer drugs, caution is exercised inhandling ABRAXANE®. The use of gloves is recommended.

Using a sterile 3 mL syringe, 1.6 mL (40 mg) of Daratumumab, MOR202, orSAR650984 25 mg/mL is withdraw and slowly injected, over a minimum of 1minute, onto the inside wall of each of the vials containing 100 mg ofABRAXANE®. Unused Daratumumab, MOR202, or SAR650984 left in the 25 mg/mLvial is discarded. Injecting the Daratumumab, MOR202, or SAR650984solution directly onto the lyophilized cake is avoided as this willresult in foaming. Using a sterile 12 mL sterile syringe, 8.4 mL of 0.9%Sodium Chloride Injection, USP, is withdraw and slowly injected, over aminimum of 1 minute, onto the inside wall of each vial containingABRAXANE® 100 mg and Daratumumab, MOR202, or SAR650984 40 mg. Once theaddition of Daratumumab, MOR202, or SAR650984 1.6 mL and 0.9% SodiumChloride Injection, USP 8.4 mL is complete in each vial, each vial isgently swirled and/or inverted slowly for at least 2 minutes untilcomplete dissolution of any cake/powder occurs. The generation of foamis avoided. The concentration of each vial is 100 mg/10 mL ABRAXANE® and40 mg/10 mL Daratumumab, MOR202, or SAR650984. The vials containing theABRAXANE® and Daratumumab, MOR202, or SAR650984 are allowed to sit for60 minutes. The vial(s) are gently swirled and/or inverted every 10minutes to continue to mix the complexes. After 60 minutes is elapsed, asterile 60- to 100-mL syringe (appropriate size for the volume beingadministered) is used to withdraw the calculated dosing volume ofABRAXANE® and Daratumumab, MOR202, or SAR650984 from each vial. Asufficient quantity of 0.9% Sodium Chloride Injection, USP is added tomake the final concentration of ABRAXANE® 5 mg/mL and Daratumumab,MOR202, or SAR650984 2 mg/mL. The syringe is gently swirled and/orinverted slowly for 1 minute to mix. The storage and stability is for upto 4 hours at room temperature following final dilution.

Administration

The IV initial complex dose is infused over 60 minutes via syringe pump.The infusion may be shortened to 30 minutes if the initial infusion iswell tolerated. Infusion is monitored closely during the infusionprocess for signs/symptoms of an infusion reaction. The patient's lineis flushed after administration with 20 mL 0.9% Sodium Chloride. Anexample calculation and preparation is as follows:

-   -   Dose level 1: ABRAXANE® 125 mg/m²/Daratumumab, MOR202, or        SAR650984 50 mg/m²    -   BSA=2 m²    -   Doses required: ABRAXANE® 250 mg/Daratumumab, MOR202, or        SAR650984 100 mg    -   Obtain three 100 mg vials of ABRAXANE®.    -   Obtain one 100 mg vial of Daratumumab, MOR202, or SAR650984 25        mg/mL.    -   Withdraw 1.6 mL (40 mg) of Daratumumab, MOR202, or SAR650984 25        mg/mL and slowly inject over 1 minute onto the inside wall of        one of the 100 mg ABRAXANE® vials. Repeat this procedure for        each of the remaining two ABRAXANE® 100 mg vials.    -   Add 8.4 mL 0.9% Sodium Chloride Injection, USP onto the inside        wall of one of the vials containing ABRAXANE® and Daratumumab,        MOR202, or SAR650984. Repeat this procedure for each of the        remaining two ABRAXANE® and Daratumumab, MOR202, or SAR650984        vials.    -   Let mixture sit for 60 minutes (swirling every 10 minutes). The        final concentration of each vial should be 100 mg ABRAXANE®/10        mL and 40 mg Daratumumab, MOR202, or SAR650984/10 mL.    -   Withdraw 25 mL from the ABRAXANE® and Daratumumab, MOR202, or        SAR650984 containing vial and place in a 100 mL sterile syringe.        Add 25 mL 0.9% Sodium Chloride Injection, USP for a final        ABRAXANE® concentration of 5 mg/mL and Daratumumab, MOR202, or        SAR650984 concentration of 2 mg/mL. Infuse via syringe pump over        60 minutes (first dose, 30 minutes subsequent doses).        Response to ABRAXANE®/Daratumumab, MOR202, or SAR650984 Complex        Treatment

Each patient's response to treatment with a ABRAXANE®/Daratumumab,MOR202, or SAR650984 complex formulation is monitored.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

What is claimed is:
 1. A method for treating a mammal having myeloma,said method comprising administering to said mammal a compositioncomprising nanoparticle/antibody complexes containing albumin-boundpaclitaxel complexed with an anti-CD38 polypeptide antibody wherein theadministration of the composition increases length of progression-freesurvival, and wherein an average diameter of said complexes is between0.1 and 0.9 μm.
 2. The method of claim 1, wherein said mammal is ahuman.
 3. The method of claim 1, wherein said myeloma is multiplemyeloma.
 4. The method of claim 1, wherein the anti-CD38 antibody isDaratumumab, MOR202, SAR650984, or any combination thereof.
 5. A methodfor treating a mammal having myeloma, wherein said method comprisesadministering, to said mammal, a composition comprisingnanoparticle/antibody complexes comprising albumin-bound paclitaxel,wherein an average diameter of said complexes is between 0.1 and 0.9 μm,and wherein said antibody is an anti-CD38 antibody.
 6. The method ofclaim 5, wherein said mammal is a human.
 7. The method of claim 5,wherein said myeloma is a multiple myeloma.
 8. The method of claim 5,wherein said myeloma is a light chain myeloma.
 9. The method of claim 5,wherein said myeloma is a non-secretory myeloma.
 10. The method of claim5, wherein the anti-CD38 antibody is Daratumumab, MOR202, SAR650984, orany combination thereof.
 11. A method for treating a mammal havingmyeloma, wherein said method comprises administering, to said mammal, acomposition comprising nanoparticle/antibody complexes comprisingalbumin-bound paclitaxel, wherein an average diameter of at least 50percent of said complexes of said composition is between 0.1 and 0.9 μm,and wherein said antibodies are anti-CD38 antibodies.
 12. The method ofclaim 11, wherein said mammal is a human.
 13. The method of claim 11,wherein said myeloma is a multiple myeloma.
 14. The method of claim 11,wherein said myeloma is a light chain myeloma.
 15. The method of claim11, wherein said myeloma is a non-secretory myeloma.
 16. The method ofclaim 11, wherein the anti-CD38 antibody is Daratumumab, MOR202,SAR650984, or any combination thereof.